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Evaluation of [(111...
Evaluation of [(111/114m)In]CHX-A''-DTPA-ZHER2:342, an affibody ligand coniugate for targeting of HER2-expressing malignant tumors
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- Orlova, Anna (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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Rosik, Daniel (author)
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- Sandström, Mattias (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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- Lundqvist, Hans (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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- Einarsson, L. (author)
- Uppsala universitet,The Svedberg-laboratoriet
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- Tolmachev, Vladimir (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: The Quarterly Journal of Nuclear Medicine and Molecular Imaging. - 1824-4785. ; 51:4, s. 314-323
- Related links:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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Abstract
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- AIM: Radionuclide imaging of the HER2 receptor, which is a target for trastuzumab therapy, can provide important diagnostic information. Further, targeting radionuclide therapy might be an option for treatment of HER2 expressing tumors. The phage-display selected Affibody ligand Z(HER2:342), which binds to HER2 with an affinity of 22 pM, may here play an important role. The small size of the Z(HER2:342), 7.5 kDa, enables quick tumor localization and fast blood clearance. Earlier, successful targeting of HER2-expressing xenografts using Z(HER2:342) labeled using [(111)In]benzyl-DTPA was reported. By changing to the CHX-A''-DTPA chelator, the stability and labeling kinetics of the radiometal-Z(HER2:342) conjugate can be improved. The aim of this study was to evaluate the labeling of the CHX-A''-DTPA-Z(HER2:342) conjugate with (111)In for diagnostic imaging and with (114m)In for locoregional radionuclide therapy. METHODS: The isothiocyanate derivative of CHX-A''-DTPA was coupled to Z(HER2:342) in alkaline conditions at 37 degrees C. The conjugate was labeled with both (111)In and (114m)In and evaluated in vitro and in vivo. RESULTS: Labeling with (111)In and (114m)In provided >95% yield after 30 min at RT. Specific radioactivity was 0.5 and 12 MBq/nmol, for (114m)In and (111)In, respectively. The radiolabeled conjugates demonstrated specific binding to HER2 expressing SKOV-3 cells. In mice bearing SKOV-3 xenografts, the tumor uptake of [(111)In]CHX-A''-DTPA-Z(HER2:342) 4 h postinjection was 10.3+/-3.6% IA/g and tumor-to-blood ratio about 190. CONCLUSION: [(111)In]CHX-A''-DTPA-Z(HER2:342) is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with (114m)In it could also be used for locoregional treatment of HER2 expressing tumors.
Keyword
- Animals
- Antibodies; Monoclonal/*pharmacokinetics/*therapeutic use
- Cell Survival/radiation effects
- Female
- Ligands
- Metabolic Clearance Rate
- Mice
- Organ Specificity
- Ovarian Neoplasms/*metabolism/radionuclide imaging/*radiotherapy
- Pentetic Acid/*analogs & derivatives/chemistry/diagnostic use/pharmacokinetics
- Radiopharmaceuticals/chemical synthesis/diagnostic use/pharmacokinetics
- Radiotherapy/*methods
- Receptor; erbB-2/*metabolism
- Recombinant Fusion Proteins/chemistry/*diagnostic use/*pharmacokinetics
- Tissue Distribution
- Treatment Outcome
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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